ACE inhibitory tetrapeptides from Amaranthus hypochondriacus 11S globulin.

Amaranth seed is a valuable source of dietary protein with very high nutritional quality, and recently its potential as a nutraceutical has been proposed. The aim of this work was to provide experimental evidence for the presence of anti-hypertensive peptides in globulin 11S, one of the major constituents of the seed, by means of an in-silico based peptide library screening method. A three-dimensional model of globulin 11S was built, upon which anti-hypertensive peptides were mapped via a database-driven method. Solvent accessibility was evaluated for each potential peptide, and two potent and exposed tripeptides were detected: IKP and LEP. An N-terminal extension of these two peptides was built using the globulin 11S primary sequence information, and ACE inhibitory behaviour was simulated by automated ligand-protein docking. The occurrence of two inhibitory tetrapeptides, ALEP and VIKP, was predicted and experimentally validated by an in vitro ACE inhibition assay that showed IC50 values of 6.32 mM and 175 microM, respectively. This study is the first to provide experimental proof of the anti-hypertensive value of Amaranth. Furthermore, this is the first time that a peptide docking approach is used to find ACE-inhibitory peptides from a food protein source.

Modified ultrafiltration reduces morbidity after adult cardiac operations: a prospective, randomized clinical trial.

BACKGROUND: Extracorporeal circulation contributes to morbidity after open-heart surgery by causing a systemic inflammatory reaction. Modified ultrafiltration is a technique able to remove the fluid overload and inflammatory mediators associated with use of cardiopulmonary bypass. It has been shown to reduce morbidity after cardiac operations in children, but the impact on adult cardiac procedures is unknown. METHODS AND RESULTS: Five hundred seventy-three consecutive adult patients were prospectively randomized to either ultrafiltration after cardiopulmonary bypass (treatment) or to no ultrafiltration (control). Parsonnet score was used to assess the severity of the patients' clinical conditions. Analysis was done with Student's t test or Mann-Whitney U test for continuous variables and Fisher's exact test or Pearson's chi(2) for discrete variables. Hospital mortality was 2.5% (7 of 284) in the treatment group versus 3.8% (11 of 289) in the control group (P=0.357). Hospital morbidity was lower in treated patients (66 of 284 [23.2%] versus 117 of 289 [40.5%], P=0.0001). Cardiac morbidity was similar (26 of 284 [9.1%] versus 35 of 289 [12.1%], P=0.251), whereas significantly lower rates of respiratory (20 of 284 [7.0%] versus 36 of 289 [12.5%], P=0.029), neurological (5 of 284 [1.8%] versus 14 of 289 [4.8%], P=0.039), and gastrointestinal (0 of 284 versus 4 of 289 [1.4%], P=0.044) complications were found in treated patients. Transfusion requirements were also lower in treated patients (1.66+/-2.6 versus 2.25+/-3.8 U/patient, P=0.039). Duration of intensive care (39.9+/-49.2 versus 46.3+/-72.8 hours, P=0.218) and hospital stay (7.6+/-3.5 versus 7.9+/-4.4 days, P=0.372) were comparable. CONCLUSIONS: Modified ultrafiltration after cardiopulmonary bypass is associated with a lower prevalence of early morbidity and lower blood transfusion requirements. The impact on length of hospital stay needs further analysis. Routine application of modified ultrafiltration after adult cardiac operations is warranted.

Stentless aortic xenograft valve replacement: lessons learned after 300 implants.

Early results after aortic valve replacement (AVR) with three different types of stentless xenografts suggested less satisfactory outcome with a simplified implant model (Cryolife-O'Brien) compared with two standard implant models (Biocor PSB, Toronto SPV). To assess the impact of experience on mid-term outcome after stentless AVR, results with 322 implants were reviewed. Between July 1992 and February 1999, 106 patients underwent operations to implant the Biocor PSB (group 1), 139 patients the Toronto SPV (group 2), and 77 patients the Cryolife-O'Brien valve (group 3). Mean age (70+/-6 years; 70+/-7 years; 71+/-7 years; P = .7), prevalence of male gender (56 patients, 53%; 72 patients, 55%; 38 patients, 49%; P = .4), prevalence of aortic stenosis (72 patients, 68%; 77 patients, 55%; 38 patients, 49%; P = .7), and need for associated procedures (51 patients, 48%; 54 patients, 39%; 33 patients, 43%; P = .7) were similar among all three groups, respectively. Mean aortic cross-clamp time was shorter in group 3 (96+/-24 min; 98+/-24 min; 78+/-22 min; P = .02). Early deaths (3/106, 3%; 4/139, 3%; 2/77; 3%, P = .8) and late survival were comparable (89%+/-5%, 93%+/-4%, and 85%+/-7% at 5 years, P = .1) among groups. Follow-up ranged from 1 to 84 months (mean 52+/-20 months). Five-year freedom from valve deterioration (95%+/-5%, 96%+/-3%, and 85%+/-7%, P = .008) and from reoperation (98%+/-2%, 98%+/-2%, 92%+/-4%, P = .01) was significantly poorer in group 3 patients. When valve failure resulting from technical mishaps (none in the last 60 implants) with the Cryolife-O'Brien valve was excluded, no significant difference in freedom from valve deterioration was noted (98%+/-2%, 96%+/-3%, and 95%+/-4%, P = .1). Late functional status of 290 survivors was satisfactory and comparable among groups (1.3+/-0.8, 1.1+/-0.4, and 1.4+/-0.7 New York Heart Association class, P = .5). After an initial learning curve, simplified implant stentless xenografts offer satisfactory mid-term results, which are comparable to two-suture-line implant valves. Owing to the shorter grafting time, simplified implant xenografts such as the Cryolife-O'Brien may be particularly suited for complex operations where associated procedures are required.

Results of Biocor stentless valve replacement for infective endocarditis of the native aortic valve.

The mid-term results in a selected group of 9 patients with native aortic valve endocarditis managed by aortic valve replacement (with or without complex annular reconstruction) using a totally biological stentless valve are outlined. At a mean follow-up of 48 months, there are currently 7 survivors (2 late noncardiac deaths) with 100% freedom from reoperation, valve-related complication, and endocarditis.

Aortic valve replacement with the Biocor PSB stentless xenograft.

BACKGROUND: The midterm clinical results after aortic valve replacement with the Biocor PSB stentless xenograft on all patients operated between October 1992 and October 1996 were reviewed. METHODS: One hundred six patients, aged 70+/-6 years, had aortic valve replacement for aortic stenosis (67%), regurgitation (11%), or both (22%). Associated procedures were done in 49 patients (46%), including coronary artery bypass in 30 patients, mitral valve repair/replacement in 16, and ascending aorta replacement in 5 patients. Aortic cross-clamp and cardiopulmonary bypass times were 96+/-24 and 129+/-31 minutes, respectively. RESULTS: There were 3 (3%) early deaths due to low output (2 patients) and cerebrovascular accident (1 patient). Follow-up of survivors ranged from 6 to 66 months (mean, 39+/-14 months). Survival was 94%+/-2% and 90%+/-3% at 1 and 5 years. There were 5 late deaths due to cardiac cause (2), cancer (2), and pulmonary embolism (1 patient). No patient had structural valve deterioration, whereas 100% and 95%+/-3% were free from valve-related events at 1 and 5 years. There were two reoperations due to narrowing of the left coronary ostium and endocarditis, with an actuarial freedom from reoperation of 99%+/-1% and 98+/-1% at 1 and 5 years, respectively. Functional results demonstrated a mean peak transprosthetic gradient of 16+/-12 mm Hg, with only 1 patient (1%) with a 55 mm Hg gradient. No cases of valve regurgitation greater than mild were recorded at follow-up. Assessment of New York Heart Association functional class demonstrated a significant improvement (2.9+/-0.6 versus 1.4+/-0.7; p=0.01). All patients were free from anticoagulation. CONCLUSIONS: Aortic valve replacement using the Biocor PSB stentless xenograft offers excellent midterm survival, negligible valve deterioration, and a very low rate of valve-related events, which are comparable to estimates reported with other models of stentless xenografts and currently available stented xenografts. Hemodynamic performance is favorable and quality of life satisfactory.

Midterm results after aortic valve replacement with freehand stentless xenografts: a comparison of three prostheses.

OBJECTIVE: The ideal substitute for the diseased aortic valve is yet to be found. For the assessment and comparison of the midterm results after aortic valve replacement with three different types of freehand stentless xenografts, all patients who underwent the operation between October 1992 and April 1997 were reviewed. METHODS: Of 231 patients undergoing aortic valve replacement, 106 patients (group 1) were given the Biocor PSB (Biocor Industria e Pesquisa Ltda, Belo Horizonte, MG, Brazil); 76 patients (group 2) were given the Toronto SPV (St. Jude Medical, Inc., St. Paul, Minn.), and 49 patients (group 3) were given the O'Brien-Angell valve (Bravo Cardiovascular model 300, Cryolife, Inc., Marietta, Ga.). The first two xenografts require inflow and outflow suturelines; the third xenograft needs a single-sutureline implantation. Mean age (70 +/- 6 years; 70 +/- 7 years; 72 +/- 9 years; p = 0.6), prevalence of male sex (56 patients, 53%; 37 patients, 49%; 22 patients, 45%; p = 0.7), of aortic stenosis (72 patients, 68%; 54 patients, 71%; 37 patients, 73%; p = 0.6), and need for associated procedures (51 patients, 48%; 30 patients, 40%; 21 patients, 43%; p = 0.1) were comparable among groups. Mean aortic crossclamp time was shorter in group 3 (96 +/- 24 minutes; 100 +/- 23 minutes; 88 +/- 25 minutes;p = 0.01). RESULTS: Early deaths were 3 of 106 (3%) in group 1, 2 of 76 (3%) in group 2, and 2 of 49 (4%) in group 3. Follow-up of survivors ranged from 1 to 54 months (mean 32 +/- 13 months). Survival at 4 years was 90% +/- 3% in group 1, 95% +/- 3% in group 2, 85% +/- 8% in group 3 (p = 0.3). At 4 years, freedom from valve-related events was 95% +/- 6%, 100%, 70% +/- 8% (p = 0.004), while freedom from valve deterioration was 99% +/- 1%, 100%, 73% +/- 8% (p = 0.001), in group 1, 2, and 3, respectively (p = 0.001). At follow-up, reintervention on the xenograft was necessary in one patient (endocarditis) in group 1, none in group 2, and six in group 3 (technical cause, group 3; valve tear, group 2; pannus, group 1). Regression analysis showed O'Brien-Angell type of xenograft to be predictive of valve-related events (p = 0.02), valve deterioration (p = 0.001), and reoperation (p = 0.001) during follow-up. CONCLUSIONS: Midterm survival after stentless aortic valve replacement is good with all three xenografts. Freedom from valve-related events, valve deterioration, and reoperation are excellent with the Biocor PSB or the Toronto SPV stentless valves but less satisfactory with the O'Brien-Angell valve.

Metabolic findings in the erythrocytes of cardiopathic and anaemic dogs.

Few data are available on the activities of canine erythrocyte enzymes and on 2,3 diphosphoglycerate (2,3DPG) concentrations in pathological conditions other than heritable erythrocyte defects. Because some diseases might affect erythrocyte metabolism and oxygen transport, we evaluated these parameters in 10 healthy dogs and in dogs with symptomless dirofilariosis (n = 9), mild (n = 13) and severe (n = 8) cardiac failure, and haemolytic anaemia (n = 8). To evaluate possible membrane damage, the osmotic fragility of the red cells was measured. No haematological abnormalities were found in the dogs with mild cardiopathy or in those with symptomless dirofilariosis. Severe anaemia and neutrophilic leucocytosis were found in the dogs with haemolytic anaemia and, to a lesser degree, in those with severe heart failure. In dogs with these two diseases, elevated values obtained were, respectively: pyruvate kinase (PK) 17.5 +/- 10.3 U/g haemoglobin (Hb) (P < 0.001) and 11.6 +/- 7.5 U/g Hb (P < 0.01); glucose-6-phosphate dehydrogenase (G6PDH) 8.9 +/- 5.4 U/g Hb (P < 0.001) and 5.6 +/- 4.2 U/g Hb; 2,3DPG 21.8 +/- 4.9 U/g Hb (P < 0.001) and 22.5 +/- 4.1 U/g Hb (P < 0.001). The increased 2,3DPG concentrations may have been due to diminished oxygen availability but the observed enzymatic changes were attributed mainly to the presence of young red blood cells: there was a positive correlation between nucleated red blood cells and PK activity, G6PDH activity and 2,3DPG concentration and a negative correlation between mature erythrocytes and PK activity, G6PDH activity and 2,3DPG concentration. This was supported by the derivative curve of the fragiligram, which showed two or three peaks corresponding to different erythrocyte populations and by the negative correlation between the maximum haemolytic NaCl concentration and the reticulocyte number. The measurement of PK and G6PDH activity and of the 2,3PG concentration, together with information provided by the fragiligram, would seem to be of value in defining the clinico-haematological picture in clinical heart diseases and haemolytic anaemia.

Hancock versus stentless bioprosthesis for aortic valve replacement in patients older than 75 years.

BACKGROUND: Stented aortic bioprostheses are routinely used in elderly patients. The stent, however, is obstructive and implies several hazards. Stentless aortic valves appear to be hemodynamically advantageous. However, their implantation is longer and technically more demanding, and durability is still under investigation. METHODS: Between January 1993 and December 1996, 77 patients (28 men) were prospectively randomized to undergo aortic valve replacement using the Hancock valves (group A: 40 patients, 16 men; age, 77+/-3 years; body surface area, 1.7+/-0.17 m2) or a stentless bioprostheses (group B: 37 patients, 12 men; age, 76+/-2 years; body surface area, 1.7+/-0.15 m2; Biocor, 17; Toronto SPV, 20). Preoperative variables were not significantly different between the two groups. Bypass time was 123+/-46 versus 133+/-51 minutes, and aortic cross-clamp time was 83+/-26 versus 95+/-24 minutes for group A and group B, respectively (not significant). Seven patients in group A (17.5%) and 5 in group B (13.5%) had enlargement of the aortic annulus. Valve size normalized to body surface area was 13.7+/-1.5 versus 14.1+/-1.6 mm/m2 for group A and group B, respectively (not significant). Eleven patients in group A (27.5%) and 5 in group B (13.5%) had concomitant myocardial revascularization. RESULTS: Overall perioperative mortality was 5% in group A (low cardiac output in 2 patients), and 8% in group B (low cardiac output in 1; major neurologic event in 2). Follow-up is 97% complete (group A, 14.5+/-10 months; group B, 18.5+/-12 months). One patient in group B died at 28 months of myocardial infarction. Actuarial survival at 12 and 24 months is 92% versus 91% and 92% versus 81% for group A and group B, respectively. At 6 months, patients in group A showed a peak transaortic gradient of 25+/-7 versus 20+/-9 mm Hg in group B. Progressive regression of left ventricular mass expressed as a percentage of preoperative value was 10.5% and 19% for group A and group B at 1 year postoperatively (not significant). CONCLUSIONS: Stentless valves represent a valuable alternative to conventional prostheses in patients older than 75 years, although no great advantages with their use emerge from this study. Continued evaluation particularly with regard to evidence of left ventricular remodeling and valve degeneration in the long term is warranted.

Reoperation on stentless aortic xenografts.

BACKGROUND: Stentless xenografts have been proposed as substitutes for the diseased aortic valve. Cases of valve failure requiring reoperation have thus far been sporadic. To establish the prevalence and outcome of reoperation on stentless aortic xenograft valves, all patients operated on between October 1992 and October 1996 were reviewed. METHODS: One hundred ninety-nine patients, 94 men and 105 women aged 70+/-7 years, had stentless aortic valve replacement for aortic stenosis (in 139), insufficiency (19), or both (38). Three prostheses were used, including the Biocor PSB (Belo Horizonte, Brazil) (106), Toronto SPV (St. Jude Medical, Inc., St. Paul, MN) (52), and O'Brien-Angell (Cryolife, Atlanta, GA) (41). While the Biocor PSB and Toronto SPV prostheses are designed to be implanted freehand with inflow and outflow suture lines, the O'Brien-Angell valve requires a single suture line. RESULTS: There were 7 (3.5%) total and 6 (3%) valve-related reoperative procedures during a follow-up extending up to 4 years (mean 26+/-20 months). All but one valve-related reoperation, due to endocarditis 36 months after implant, were early (less than 12 months after initial operation). Prevalence of valve-related reinterventions was 1%, 0%, and 12%, and freedom from reoperation at 3 years was 98%+/-2%, 100%, and 81%+/-8%, in patients receiving the Biocor PSB, Toronto SPV, and O'Brien-Angell valves, respectively (p = 0.0039). Cause of reoperation was technical in 3 (O'Brien-Angell), pannus in-growth in 1 (O'Brien-Angell), valve tear in 1 (O'Brien-Angell), and endocarditis in 1 (Biocor PSB). All patients survived replacement of the xenograft with a stented bioprosthesis (5) or homograft root (1) and were discharged after a mean hospital stay of 6+/-3 days (range, 4 to 12 days). At follow-up 15+/-8 months after reintervention (range, 6 to 34 months), all patients are symptom-free with no evidence of recurrent valve obstruction, regurgitation, or infection. CONCLUSIONS: Reoperation for stentless xenograft failure is a rare overall event. Implant of the O'Brien-Angell valve may be associated with a higher prevalence of early reintervention because of nonstructural failure. When needed, reoperation on a stentless xenograft is generally a simple procedure and carries a low surgical risk.